This is a competing renewal for a Sexually Transmitted Diseases Topical Microbicide Cooperative Research Center (STD TM CRC). A total of six projects are included, including studies on the STD pathogens N gonorrhoeae, H ducreyi and T vaginalis; epidemiological studies of gonorrhea and syphilis in North Carolina; and clinical and epidemiological studies of the role of HSV and other STDs in facilitation of sexual acquisition of HIV in Malawi. These projects will be supported by an Administrative Core and a Microbiology Core. These studies will unite the scientific areas of basic microbiology and immunology with clinical infectious diseases and epidemiology. There are multiple interactions of the scientific disciplines of molecular genetics, immunology, epidemiology, biostatistics and mathematical modeling. The proposed work is an outgrowth of the current UNC STDCRC but five of the six projects are new. Project 1 studies the interaction between STDs (particularly HSV) and acquisition of HIV in Malawi. Project 2 examines the immunobiology of outer membrane proteins in H ducreyi and their potential roles in virulence and vaccines. Project 3 investigates the potential of a gonococcal outer membrane protein PilC as a vaccine candidate. Project 4 examines the potential of several other outer membrane proteins of Neisseria gonorrhoeae as a target for topical microbicides or vaccines, using a mouse female genital tract model of infection. Project 5 focuses on developing a molecular typing system for T vaginalis; this will enable future epidemiological studies of Trichomonas treatment, reinfection, and disease. Project 6 investigates novel spatial mapping and mathematical strategies for disease control and outbreak investigation, using syphilis and gonorrhea in rural NC as the index infections. The overall theme uniting each of these projects is development of novel methods for prevention of STDs.